Our work in this project is concerned with identifying discrete functions of the polyoma virus middle and small tumor antigens as they relate to virus replication and transformation of cells in culture, and to replication and induction Of tumors in the mouse. The first group of Aims focuses on the middle T antigen as the major transforming protein, its role in binding phospholipase C, the possible importance of its serving as a substrate for a cyclin dependent protein kinase, and the possible role of a proline-rich segment of the protein in transducing signals via SH3 or other cellular proteins. The second group of Aims focuses on the small T protein and particularly on the behavior of a virus mutant blocked in expression of this protein. The role of specific sequences involved in binding the phosphatase PP2A, or the DNA-J domain, will be studied. This project relates to the larger framework of the Program Project Grant which brings together an interactive group of investigators all concerned with studying oncoprotein functions of DNA-containing tumor viruses.